title: Association between alcohol consumption and plasma fetuin-A and its contribution to incident type 2 diabetes in women.
abstract: OBJECTIVE
  The benefits of moderate alcohol consumption for type 2 diabetes have been postulated to involve a mechanism of improved insulin sensitivity. Fetuin-A, which is known to inhibit insulin signalling, has emerged as a biomarker for diabetes risk. Alcohol consumption may influence circulating fetuin-A concentrations and subsequently diabetes risk by altering the insulin signal. We therefore hypothesised that moderate alcohol consumption would be associated with lower fetuin-A concentration and that fetuin-A would partly explain the association between alcohol consumption and incident type 2 diabetes.
  
  
  METHODS
  Among diabetes-free female participants in the Nurses' Health Study (n = 1,331), multiple linear regression was conducted to assess the association between alcohol consumption and plasma fetuin-A. Least-squares means (lsmeans) of fetuin-A were estimated in categories of alcohol consumption (0, 0.1-4.9, 5-14.9 and ≥ 15 g/day). The proportion of alcohol consumption and diabetes association explained by baseline fetuin-A was assessed in 470 matched incident diabetes case-control pairs with follow-up 2000-2006.
  
  
  RESULTS
  Higher alcohol consumption was associated with lower plasma fetuin-A (p for trend = 0.009): lsmean ± SE 476.5 ± 5.9 μg/ml for abstainers, 468.9 ± 5.2 μg/ml for 0.1-4.9 g/day consumers, 455.9 ± 7.0 μg/ml for 5.0-14.9 g/day consumers, and 450.0 ± 9.4 μg/ml for ≥ 15.0 g/day consumers. Fetuin-A and fasting insulin explained 18.4% and 54.8%, respectively, of the inverse association between alcohol consumption and diabetes after multiple adjustment (both p for contribution <0.04).
  
  
  CONCLUSIONS
  Moderate alcohol consumption is associated with lower plasma fetuin-A in diabetes-free women. Fetuin-A and insulin explain a significant proportion of the association between alcohol consumption and incident type 2 diabetes. Further studies are needed to examine potential biological mechanisms underlying this association.
authors.affiliation: Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA, 02115, USA.
authors.forename: Sylvia H
authors.initials: SH
authors.lastname: Ley
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.forename: Monik C
authors.initials: MC
authors.lastname: Jimenez
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Rexrode
authors.forename: Joann E
authors.initials: JE
authors.lastname: Manson
authors.forename: Majken K
authors.initials: MK
authors.lastname: Jensen
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000378:metabolism*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008875:Middle Aged; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism*
chemical_list: D007328:Insulin; D060749:alpha-2-HS-Glycoprotein